4MQ1

The crystal structure of DYRK1a with a bound pyrido[2,3-d]pyrimidine inhibitor

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d4mq1b_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4mq1c_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4mq1d_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4mq1a_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Protein kinase-like (PK-like)	8079155	3000066	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Protein kinase-like (PK-like)	8079155	3000066	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Protein kinase-like (PK-like)	8079155	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8079155	3000066	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	Pkinase_Tyr	e4mq1B1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)
C	Pkinase_Tyr	e4mq1C1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)
D	Pkinase_Tyr	e4mq1D1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)
A	Pkinase_Tyr	e4mq1A1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
B	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
C	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
C	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
D	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
D	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Dual specificity tyrosine-phosphorylation-regulated kinase 1A	protein serine/threonine/tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups cytoskeletal protein binding protein binding binding tubulin binding transcription coactivator activity transcription regulator activity protein serine/threonine/tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups cytoskeletal protein binding protein binding binding tubulin binding transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity protein serine/threonine kinase activity histone H3T45 kinase activity histone H3 kinase activity histone modifying activity histone kinase activity tau-protein kinase activity protein serine kinase activity protein tyrosine kinase activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding non-membrane spanning protein tyrosine kinase activity tau protein binding actin binding RNA polymerase II CTD heptapeptide repeat modifying activity RNA polymerase II CTD heptapeptide repeat kinase activity identical protein binding	regulation of cellular process negative regulation of biological process regulation of mRNA splicing, via spliceosome mRNA processing regulation of primary metabolic process nucleobase-containing compound metabolic process regulation of RNA metabolic process negative regulation of mRNA splicing, via spliceosome negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process RNA processing negative regulation of mRNA processing regulation of biological process negative regulation of metabolic process regulation of cellular process negative regulation of biological process regulation of mRNA splicing, via spliceosome mRNA processing regulation of primary metabolic process nucleobase-containing compound metabolic process regulation of RNA metabolic process negative regulation of mRNA splicing, via spliceosome negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process RNA processing negative regulation of mRNA processing regulation of biological process negative regulation of metabolic process primary metabolic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process negative regulation of RNA metabolic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process negative regulation of mRNA metabolic process negative regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of mRNA processing RNA splicing biological regulation regulation of macromolecule metabolic process gene expression nucleobase-containing compound biosynthetic process regulation of RNA splicing mRNA metabolic process macromolecule biosynthetic process nucleic acid metabolic process negative regulation of RNA splicing RNA splicing, via transesterification reactions negative regulation of biosynthetic process mRNA splicing, via spliceosome cellular process RNA splicing, via transesterification reactions with bulged adenosine as nucleophile regulation of mRNA metabolic process protein phosphorylation protein autophosphorylation phosphorylation peptidyl-tyrosine modification peptidyl-tyrosine autophosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process protein metabolic process peptidyl-tyrosine phosphorylation protein modification process phosphorus metabolic process rhythmic process circadian rhythm regulation of cytoskeleton organization regulation of microtubule polymerization or depolymerization regulation of cellular component organization microtubule cytoskeleton organization cellular component organization cellular component biogenesis regulation of protein-containing complex assembly cellular component assembly microtubule polymerization or depolymerization protein-containing complex assembly negative regulation of protein polymerization negative regulation of supramolecular fiber organization cellular component organization or biogenesis protein polymerization negative regulation of cellular component organization negative regulation of microtubule polymerization or depolymerization protein-containing complex organization negative regulation of cytoskeleton organization regulation of microtubule-based process negative regulation of microtubule polymerization microtubule polymerization regulation of cellular component biogenesis regulation of organelle organization negative regulation of protein-containing complex assembly organelle organization negative regulation of organelle organization regulation of protein polymerization regulation of microtubule polymerization regulation of supramolecular fiber organization microtubule-based process supramolecular fiber organization cytoskeleton organization regulation of microtubule cytoskeleton organization cellular response to stimulus response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction regulation of cellular response to stress regulation of signal transduction DNA damage response, signal transduction by p53 class mediator intracellular signal transduction negative regulation of cell communication cell communication cellular response to stress regulation of intracellular signal transduction response to stress regulation of response to stress regulation of signal transduction by p53 class mediator negative regulation of DNA damage response, signal transduction by p53 class mediator signal transduction regulation of DNA damage response, signal transduction by p53 class mediator negative regulation of signal transduction by p53 class mediator regulation of signaling negative regulation of response to stimulus signal transduction by p53 class mediator negative regulation of signal transduction regulation of response to stimulus DNA damage response regulation of cell communication signal transduction in response to DNA damage peptidyl-threonine modification peptidyl-threonine phosphorylation amyloid precursor protein catabolic process amyloid-beta metabolic process amide metabolic process amyloid precursor protein metabolic process amyloid-beta formation positive regulation of biological process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process positive regulation of gene expression positive regulation of RNA splicing developmental process multicellular organism development multicellular organismal process anatomical structure development nervous system development system development peptidyl-serine modification peptidyl-serine phosphorylation positive regulation of DNA-templated transcription DNA-templated transcription regulation of RNA biosynthetic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription peptidyl-serine autophosphorylation negative regulation of DNA methylation-dependent heterochromatin formation negative regulation of heterochromatin formation negative regulation of chromatin organization chromatin organization chromatin remodeling regulation of heterochromatin formation heterochromatin formation regulation of chromatin organization epigenetic regulation of gene expression constitutive heterochromatin formation DNA methylation-dependent constitutive heterochromatin formation negative regulation of gene expression, epigenetic regulation of protein modification process positive regulation of protein deacetylation positive regulation of protein metabolic process macromolecule deacylation protein deacetylation positive regulation of protein modification process regulation of protein deacetylation regulation of protein metabolic process protein deacylation	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection cytoplasm cytoskeleton membraneless organelle intracellular membraneless organelle axon protein-containing complex ribonucleoprotein complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B, C, D	IPR050494	Serine/threonine and dual-specificity kinase	Family
A, B, C, D	IPR000719	Protein kinase domain	Domain
A, B, C, D	IPR044131	Dual specificity tyrosine-phosphorylation-regulated kinase 1A/1B, catalytic domain	Domain
A, B, C, D	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q13627	DYRK1A-related intellectual disability syndrome intellectual disability Neurodevelopmental Disorders Down syndrome acute myeloid leukemia cerebrovascular disorder microcephaly ovarian cancer attention deficit hyperactivity disorder, inattentive type dermatomyositis epilepsy juvenile dermatomyositis pancreatic intraductal papillary-mucinous neoplasm autism spectrum disorder lymphoplasmacytic lymphoma DYRK1A-related intellectual disability syndrome intellectual disability Neurodevelopmental Disorders Down syndrome acute myeloid leukemia cerebrovascular disorder microcephaly ovarian cancer attention deficit hyperactivity disorder, inattentive type dermatomyositis epilepsy juvenile dermatomyositis pancreatic intraductal papillary-mucinous neoplasm autism spectrum disorder lymphoplasmacytic lymphoma osteosarcoma plasma cell myeloma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A, B, C, D	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.